Carbon catabolite regulation of the conversion of penicillin N into cephalosporin C.

Abstract

Cephalosporin C biosynthesis by Cephalosporium acremonium was delayed until most glucose in the medium was used. Addition of increasing concentrations of glucose up to 55 g/l decreased cephalosporin C biosynthesis but stimulated growth. Sequential formation of penicillin N (an intermediate in the cephalosporin C biosynthetic pathway) and cephalosporin C was found when the culture was developed synchronously. Little cephalosporin C formation was observed until most penicillin N had already been formed. The sequential formation of penicillin N, synthetase system and the cephalosporin C synthetase system. Cells grown in the presence of glucose showed an increased accumulation of penicillin N and clear reduction of the conversion of penicillin N to cephalosporin C. Resting cell studies indicated that the glucose effect was due to the repression of .gtoreq. 1 of the enzymes converting penicillin N into cephalosporin C. Little inhibition by glucose of the activity of these enzymes, once formed, was observed. Glucose did not significantly effect the pool sizes of precursor amino acids of cephalosporin (.alpha.-aminoadipic acid and valine) or methionine (an inducer of penicillin N and cephalosporin C biosynthesis). Evidently, glucose catabolism specifically represses the enzyme system converting penicillin N into cephalosporin C.